Abstracts Biological Sciences

Regulation of transglutaminase factor XIIIa by collagen type I in MC3T3-E1/C14 osteoblasts

by Sarah Piercy

The integrity of bone is essential for normal function throughout life, because it provides a hard matrix on which the soft tissues can operate; facilitating protection of body organs, storage of micronutrients, and locomotion. Bone itself begins as a soft tissue secreted by the bone forming cells, the osteoblasts: these cells secrete the soft matrix and then regulate its mineralization to the hard skeleton. However, before mineralization can occur, the soft matrix, or “osteoid” secreted by the osteoblasts must be of proper microstructure such that the mature bone is formed on an underlying matrix that can withstand the tensile forces and storage requirements that will be placed upon it. Crosslinking of the extracellular matrix components by a class of enzymes, the transglutaminases, is thought to play an important role in assuring the quality of osteoid before mineralization occurs. The transglutaminases are a family of calcium-dependent enzymes that can stabilize protein networks by covalent crosslinks between glutamine side chains and lysines or other primary amines. Previous studies have indicated that the transglutaminases TG2 and FXIIIa are expressed in bone, and that they are capable of crosslinking components of the osteoid such as fibronectin and collagen in vitro. This study sought to identify elements regulating transglutaminase expression and cross-linking activity in maturing cultures of mouse calvarial preosteoblasts. The data confirm previous findings that FXIIIa, but not TG2, is externalized in differentiating osteoblasts. Newly realized is that this externalization is due to concurrent collagen type I secretion and deposition, and not due to direct affects of AA. Furthermore, externalization is required by the MAPK-pathway, but is apparently not mediated through collagen signaling via its receptor, the α2β1 integrin. In addition, collagen was found to not be a glutamine substrate donor for the transglutaminase-mediated crosslinking r La santé et l'intégrité du tissu osseux représentent un attribut essentiel pour le bon fonctionnement de l'organisme tout au long de sa vie. Le tissu osseux fournit à l'organisme une structure dure et solide au moyen de laquelle l'ensemble de la matière organique et les tissus biologiques mous peuvent fonctionner correctement. La structure robuste et fonctionnelle de l'os facilite la protection des organes du corps et l'entreposage des éléments nutritifs et joue un rôle décisif dans la locomotion. L'os naît sous forme d'un tissu mou appelé tissu ostéoïde élaboré comme produit de sécrétion des cellules génératrices de tissu osseux, à savoir les ostéoblastes. Ces cellules secrètent la matière organique molle qui sera ensuite minéralisée à la suite de l'action coopérative concertée des protéines et d'autres biomolécules pour former la matière dure du squelette. Cependant, avant que la minéralisation soit commencée le tissu ostéoïde mou sécrété par les ostéoblastes doit posséder une microstructure appropriée de telle sorte que l'os mature soit développé sur un…